Affinage

USP26

Ubiquitin carboxyl-terminal hydrolase 26 · UniProt Q9BXU7

Length
913 aa
Mass
104.0 kDa
Annotated
2026-06-11
45 papers in source corpus 27 papers cited in narrative 27 extracted findings
Cross-family judge vs UniProt: tie faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

USP26 is an X-linked deubiquitinating enzyme that controls the abundance of diverse regulatory proteins by cleaving ubiquitin chains and shielding substrates from proteasomal degradation, with prominent roles in male germ cell development, genome maintenance, and signaling control (PMID:20501646, PMID:33978233). Its catalytic activity depends on a core USP domain whose integrity is required for substrate cleavage (PMID:29111204). In the nucleus, USP26 binds androgen receptor through nuclear-receptor interaction motifs and stabilizes it by reversing hormone-induced ubiquitination, thereby tuning AR transcriptional output (PMID:20501646). During meiosis it localizes to the XY body and stabilizes TEX11 to enforce proper sex-chromosome pairing, and its loss produces XY-aneuploid spermatozoa (PMID:33978233). USP26 acts as a regulator of signaling feedback by deubiquitinating and stabilizing SMAD7 within a TGF-β negative feedback loop (PMID:28381482), and it amplifies its own expression through a feed-forward loop with RNF12 in which it blocks RNF12 autoubiquitylation, an axis required for gametogenesis gene expression (PMID:35857630). At DNA double-strand breaks USP26 removes RNF168-induced ubiquitin conjugates, restrains RAP80-BRCA1 spreading, and promotes BRCA1-PALB2 association to enable homologous recombination (PMID:26101254). Across multiple cancer and stem-cell contexts USP26 stabilizes a broad substrate set including PRC1 components CBX4/CBX6 (PMID:28839133), Snail (PMID:30763716), TAZ (PMID:35397626), SIRT1 (PMID:39251623), and SIRT2 (PMID:39377219), and its enzymatic activity is itself regulated—suppressed by elevated cellular ROS (PMID:32235588) and enhanced toward BAG3 by Tip60-mediated acetylation (PMID:38880224). Whether USP26 is essential for mouse fertility is unresolved within the corpus: one knockout study reports background-dependent sterility and meiotic defects (PMID:31551464) while two independent null lines show normal fertility (PMID:30887115).

Mechanistic history

Synthesis pass · year-by-year structured walk · 20 steps
  1. 2010 High

    Established USP26's first molecular function: that it is a nuclear DUB acting on a defined substrate (AR) rather than an orphan enzyme.

    Evidence shRNA screen, reciprocal Co-IP, subnuclear foci imaging, and ubiquitination assay

    PMID:20501646

    Open questions at the time
    • Did not define the linkage type removed from AR
    • Physiological context of AR regulation not addressed
  2. 2014 Medium

    Placed USP26 in a tissue context by showing AR colocalization predominantly in human Leydig cell nuclei, linking the AR interaction to testis biology.

    Evidence Immunofluorescence colocalization in human testis tissue

    PMID:24922532

    Open questions at the time
    • Colocalization is correlative, not functional
    • Single-lab tissue study
  3. 2015 High

    Revealed a genome-maintenance role distinct from transcriptional regulation: USP26 trims RNF168-dependent ubiquitin at DSBs to channel repair toward homologous recombination.

    Evidence Genetic screen, DSB immunofluorescence, RAP80 double-knockdown epistasis, and HR reporter assay

    PMID:26101254

    Open questions at the time
    • Direct DSB substrate of the DUB activity not biochemically defined
    • Recruitment mechanism to breaks unknown
  4. 2017 High

    Defined USP26 as a node in TGF-β negative feedback by showing it stabilizes SMAD7 to dampen receptor signaling.

    Evidence Co-IP, ubiquitination assay, siRNA knockdown with p-SMAD2 and receptor readouts

    PMID:28381482

    Open questions at the time
    • Ubiquitin linkage specificity on SMAD7 not resolved
    • In vivo relevance not tested
  5. 2017 High

    Connected USP26 to chromatin/pluripotency control by demonstrating K48-specific deubiquitination and stabilization of PRC1 components CBX4/CBX6 that repress pluripotency genes.

    Evidence K48-linkage-specific ubiquitination assay, Co-IP, ChIP for H2A ubiquitination, reprogramming assay

    PMID:28839133

    Open questions at the time
    • Whether USP26 directly contacts both CBX proteins versus the assembled PRC1 not separated
  6. 2017 Medium

    Mapped the catalytic requirement: identified Q156 as essential for DUB activity and showed each domain half alone is inactive, defining the functional core.

    Evidence In vitro USP cleavage assay with site-directed mutagenesis on model substrates

    PMID:29111204

    Open questions at the time
    • No structural model of the active site
    • Activity tested only on model substrates
  7. 2016 Medium

    Extended the substrate repertoire to Mdm2 and showed USP26 itself is subject to ubiquitination, hinting at autoregulation of the DUB.

    Evidence Co-transfection, Co-IP, cell-free ubiquitination, and half-life analysis

    PMID:27810359

    Open questions at the time
    • E3 ligase ubiquitinating USP26 not identified
    • Single study without functional downstream readout
  8. 2016 Medium

    Linked a disease-associated variant to function by showing the R344W mutation abolishes AR deubiquitination and binding, providing a genotype-mechanism connection.

    Evidence Immunoprecipitation, ubiquitination assay, luciferase reporter in HeLa and TM4 cells

    PMID:27089915

    Open questions at the time
    • Clinical penetrance of R344W not established here
    • Single-lab study
  9. 2019 High

    Confronted USP26's role in fertility with conflicting in vivo data: background-dependent meiotic failure in one model versus no phenotype in two independent null lines.

    Evidence Independent mouse knockout lines with spermatocyte cytology, histology, and fertility assessment

    PMID:30887115 PMID:31551464

    Open questions at the time
    • Genetic-background modifiers not identified
    • Reason for discordance between knockout lines unresolved
  10. 2019 Medium

    Broadened the oncogenic substrate set by showing USP26 stabilizes the EMT driver Snail to promote carcinoma migration and invasion.

    Evidence DUB library screen, Co-IP, ubiquitination assay, migration/invasion assays

    PMID:30763716

    Open questions at the time
    • Linkage specificity on Snail not defined
    • Single-lab study
  11. 2020 Medium

    Showed USP26 activity is environmentally tuned: elevated ROS suppresses its DUB activity, destabilizing AR/ARv7 and sensitizing prostate cancer cells to enzalutamide.

    Evidence In vitro DUB activity assay, ROS measurement, ubiquitination assay

    PMID:32235588

    Open questions at the time
    • Molecular basis of ROS sensitivity (e.g. cysteine oxidation) not mapped
    • Single study
  12. 2020 Medium

    Positioned USP26 downstream of RAC1B in the SMAD7/TGF-β axis and as an AR-pathway driver of Leydig cell proliferation, integrating it into upstream signaling control.

    Evidence RNAi epistasis with promoter reporters and migration assays; Co-IP with cell-cycle flow cytometry

    PMID:32545415 PMID:33064378

    Open questions at the time
    • Leydig cell study is Low confidence with limited mechanistic depth
    • Direct versus indirect transcriptional induction of USP26 not separated
  13. 2021 High

    Defined the meiotic mechanism: USP26 localizes to the XY body and stabilizes TEX11 to ensure sex-chromosome pairing, with loss producing XY-aneuploid sperm and Klinefelter offspring.

    Evidence Mouse knockout, XY-body immunofluorescence, TEX11 stability assays, clinical sperm FISH aneuploidy analysis

    PMID:33978233

    Open questions at the time
    • Reconciliation with the no-phenotype knockout lines not resolved
    • Linkage type removed from TEX11 not specified
  14. 2022 High

    Uncovered a self-amplifying circuit: RNF12 de-represses Usp26 transcription, and USP26 in turn blocks RNF12 autoubiquitylation, forming a feed-forward loop required for gametogenesis gene expression.

    Evidence Quantitative proteomics, reciprocal Co-IP, ubiquitination assay, ESC differentiation, patient-variant mutagenesis

    PMID:35857630

    Open questions at the time
    • Quantitative thresholds of the loop not modeled
    • How disease variants quantitatively perturb the loop incompletely defined
  15. 2022 Medium

    Added the Hippo effector TAZ as an activity-dependent substrate, linking USP26 to TAZ/TEAD target gene expression in anaplastic thyroid cancer.

    Evidence Co-IP, ubiquitination assay, catalytic-mutant rescue, siRNA with target-gene readout

    PMID:35397626

    Open questions at the time
    • Single-lab study
    • Whether TAZ regulation occurs outside thyroid cancer not tested
  16. 2023 Medium

    Identified KLF6 as a USP26 substrate via domain-mapped interaction (residues 285-913), with stabilization restraining cell proliferation and migration.

    Evidence DUB library screen, Co-IP with domain mapping, half-life and ubiquitination assays, functional cellular assays

    PMID:38064851

    Open questions at the time
    • Single study
    • Physiological tissue context not addressed
  17. 2024 Medium

    Showed USP26 regulates mitophagy and antiviral immunity through site- and linkage-specific deubiquitination of PRKN (K129) and TRAF3 (K63), and is itself activated toward BAG3 by Tip60 acetylation at K134.

    Evidence Co-IP, site/linkage-specific ubiquitination assays, mutagenesis (K129R, K134), acetylation assay, mitophagy and IFN-β/ISG reporter assays

    PMID:38565942 PMID:38880224 PMID:39058724

    Open questions at the time
    • Each substrate documented in a single study
    • Cross-pathway coordination among these substrates not examined
  18. 2024 High

    Tied USP26 to cancer cell survival via virus- and hypoxia-driven transcription and stabilization of SIRT1 and SIRT2, controlling proliferation, apoptosis, and mitochondrial function.

    Evidence DUB/sgRNA library screens, Co-IP, ubiquitination assays, in vivo KO, promoter binding/ChIP, mitochondrial assays

    PMID:39251623 PMID:39377219

    Open questions at the time
    • Whether SIRT1 and SIRT2 are regulated in the same cells not addressed
    • Linkage specificity on SIRT2 not fully defined
  19. 2025 Medium

    Revealed osteoblast-intrinsic roles via conditional knockout: USP26 sustains an H3K18-lactylation/KSRP/FSTL1 splicing axis and stabilizes IL4I1 to support tryptophan metabolism and B lymphopoiesis, with systemic metabolic and immune consequences.

    Evidence Osteoblast-specific conditional KO mice, ChIP (H3K18LA), splicing RT-PCR, targeted metabolomics, immune phenotyping

    PMID:41417635 PMID:41687771

    Open questions at the time
    • Mechanism connecting USP26 DUB activity to H3K18 lactylation not direct
    • Single-lab conditional KO findings
  20. 2025 Low

    Added c-Myc stabilization driving aerobic glycolysis in gastric cancer to the substrate list.

    Evidence Co-IP, ubiquitination assay, shRNA knockdown, glycolysis/proliferation assays

    PMID:41125405

    Open questions at the time
    • Single Co-IP/ubiquitination assay with limited mechanistic depth
    • No structural or linkage characterization

Open questions

Synthesis pass · forward-looking unresolved questions
  • How a single DUB selects among this very broad substrate set and how its tissue-restricted, ROS- and acetylation-regulated activity is coordinated in vivo remains unresolved, as does the discordance between knockout phenotypes.
  • No structural basis for substrate selectivity
  • No unified model reconciling fertile versus sterile knockout lines
  • Substrate-recruitment determinants largely undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 11 GO:0016787 hydrolase activity 3 GO:0098772 molecular function regulator activity 3
Localization
GO:0005634 nucleus 2 GO:0005654 nucleoplasm 1
Pathway
R-HSA-392499 Metabolism of proteins 4 R-HSA-162582 Signal Transduction 3 R-HSA-1474165 Reproduction 2 R-HSA-168256 Immune System 2 R-HSA-73894 DNA Repair 1
Partners
ARBAG3MDM2PRKNRNF12SMAD7TEX11TRAF3
Complex memberships
RNF12-USP26 feed-forward complex

Evidence

Reading pass · 27 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2010 USP26 is a nuclear protein that binds to androgen receptor (AR) via three nuclear receptor interaction motifs, modulates AR ubiquitination, and stabilizes AR by counteracting hormone-induced ubiquitination, thereby influencing AR transcriptional activity. USP26 assembles with AR and other cofactors in subnuclear foci. shRNA library screen, Co-IP, subnuclear foci imaging, ubiquitination assay Molecular cancer research : MCR High 20501646
2015 USP26 is recruited to DNA double-strand breaks (DSBs) where it removes RNF168-induced ubiquitin conjugates, limits excessive spreading of RAP80-BRCA1 from DSBs, and promotes BRCA1 association with PALB2, thereby facilitating homologous recombination. Depletion of USP26 disrupts HR execution, and this effect is rescued by simultaneous depletion of RAP80. Genetic screen, siRNA depletion, immunofluorescence at DSBs, epistasis (double knockdown rescue), HR reporter assay Nucleic acids research High 26101254
2017 USP26 deubiquitinates and stabilizes SMAD7, functioning as a component of the TGF-β negative feedback loop. TGF-β enhances USP26 expression; USP26 limits ubiquitin-mediated turnover of SMAD7, preventing TGF-β receptor stabilization and reducing p-SMAD2 levels. Knockdown of USP26 degrades SMAD7, stabilizes TGF-β receptor, and enhances TGF-β signaling. Co-IP, ubiquitination assay, siRNA knockdown, western blot for p-SMAD2 and receptor levels EMBO reports High 28381482
2017 USP26 negatively regulates somatic cell reprogramming by stabilizing PRC1 complex components CBX4 and CBX6 through removal of K48-linked polyubiquitination. Accumulated CBX4 and CBX6 repress pluripotency genes (Sox2, Nanog) by ubiquitinating histone H2A at their promoters via PRC1 complexes. Co-IP, ubiquitination assay (K48-linkage specific), reprogramming efficiency assay, ChIP for H2A ubiquitination at promoters, siRNA/overexpression Nature communications High 28839133
2016 USP26 binds to Mdm2 through its coiled-coil C-terminal domain, deubiquitinates Mdm2, and stabilizes it. USP26 itself can be ubiquitinated in cell-free HeLa extract. Co-transfection, Co-IP, cell-free ubiquitination assay, half-life analysis Biochemical and biophysical research communications Medium 27810359
2016 The USP26 R344W missense mutation reduces USP26 binding affinity to AR and abolishes its deubiquitinating activity toward AR, thereby eliminating the inhibitory effect of USP26 on AR transcriptional activity in HeLa and TM4 cells. Immunoprecipitation, ubiquitination assay, luciferase transcriptional activity assay Reproductive sciences Medium 27089915
2019 USP26 deubiquitinates and stabilizes Snail, a transcription factor promoting epithelial-mesenchymal transition (EMT), and promotes esophageal squamous cell carcinoma cell migration and invasion. Identified by screening a DUB library. DUB library screen, Co-IP, ubiquitination assay, cell migration/invasion assay Cancer letters Medium 30763716
2019 Usp26 mutant male mice (DBA/2 background, but not C57BL/6) are sterile or subfertile with atrophic testes, reduced spermatids, malformed sperm head morphology, unsynapsed chromosomes in pachynema, and defective chiasma formation in diplonema, leading to apoptosis of metaphase spermatocytes. Effects are genetic-background dependent. Mouse knockout (gene-targeted mutation), histology, spermatocyte cytology (chromosome spread), fertility assessment Scientific reports High 31551464
2019 Two independently generated Usp26-null mouse lines show no overt phenotype: both males and females are fertile, with normal spermatocyte synapsis, chromosome dynamics, DNA repair, recombination, and cell-type distribution in testes. USP26 is thus not essential for mouse gametogenesis. Mouse knockout (two independent null alleles), cytology, histopathology, fertility assessment Chromosoma High 30887115
2021 USP26 protein localizes to the XY body during meiosis. Knockout of Usp26 in male mice causes incomplete sex chromosome pairing by destabilizing TEX11, leading to XY aneuploid spermatozoa and 41,XXY (Klinefelter syndrome) offspring. USP26 variants in men increase the proportion of XY aneuploid spermatozoa. Mouse knockout, immunofluorescence (XY body localization), Co-IP/western blot (TEX11 destabilization), clinical sperm FISH aneuploidy analysis The EMBO journal High 33978233
2022 RNF12 relieves REX1-mediated repression of Usp26, increasing USP26 abundance. USP26 then forms complexes with RNF12 and prevents RNF12 autoubiquitylation and proteasomal degradation, establishing a transcriptional feed-forward amplification loop. This RNF12-USP26 axis operates in mouse testes and is required for gametogenesis gene expression and germ cell differentiation. RLIM (RNF12) and USP26 disease-associated variants disrupt this axis. Quantitative proteomics (global), Co-IP, ubiquitination assay, ESC differentiation assay, mutagenesis with patient variants Science signaling High 35857630
2022 USP26 interacts with, deubiquitylates, and stabilizes TAZ (a Hippo pathway effector) in anaplastic thyroid cancer cells in a deubiquitylation activity-dependent manner. USP26 depletion decreases TAZ protein levels and reduces expression of TAZ/TEAD target genes (CTGF, ANKRD1, CYR61). Co-IP, ubiquitination assay, catalytic mutant (activity-dependent rescue), siRNA knockdown with target gene expression readout Cell death & disease Medium 35397626
2017 The USP26 Q156H mutant has no enzymatic (deubiquitinase) activity toward model substrates Ub-Met-β-gal and GST-Ub52. Eighteen other tested mutants (including E174# and E189# truncation mutants) retain wild-type enzymatic activity. Artificially constructed truncation fragments (each half alone) lose activity. In vitro USP cleavage assay with site-directed mutagenesis Gene Medium 29111204
2015 Five frequent USP26 mutations (c.363_364insACA, c.494T>C, c.1423C>T, c.1090C>T, c.1737G>A) do not affect USP26 deubiquitinase enzymatic activity in a USP cleavage assay. In vitro USP cleavage assay Andrology Medium 25755145
2024 USP26 directly interacts with PRKN (Parkin), deubiquitinates PRKN at the K129 site, and reduces its activity, thereby restraining PRKN-mediated mitophagy. A K129R mutation on PRKN diminishes its activation and mitophagy capacity. Co-IP, ubiquitination assay (site-specific K129), site-directed mutagenesis (K129R), mitophagy assay Oncogene Medium 38565942
2024 HBV-encoded HBx binds to the USP26 promoter and induces USP26 expression. USP26 then associates with SIRT1 and stabilizes it by deubiquitination, promoting HCC cell proliferation and inhibiting apoptosis. sgRNA DUB library screen, Co-IP, ubiquitination assay, murine Usp26 KO model, promoter binding assay Nature communications High 39251623
2024 USP26 deubiquitinates and stabilizes SIRT2 in BMSCs; loss of USP26 leads to SIRT2 ubiquitin-mediated degradation, causing mitochondrial dysfunction and BMSC senescence. HIF-1α promotes USP26 transcription by binding to the -191 to -198 bp and -262 to -269 bp regions of the USP26 promoter. Co-IP, ubiquitination assay, mitochondrial function assay, promoter-reporter assay, ChIP Advanced science Medium 39377219
2024 USP26 suppresses type I interferon signaling by physically interacting with TRAF3 and removing K63-linked polyubiquitination from TRAF3, thereby inhibiting the MAVS/TBK-1/IRF3 antiviral signaling pathway. USP26 knockdown enhances IFN-β and ISG expression and inhibits EV71 replication. Co-IP, linkage-specific ubiquitination assay (K63), siRNA knockdown, IFN-β/ISG reporter assay, viral replication assay PloS one Medium 39058724
2024 USP26 interacts with and deubiquitinates BAG3, increasing its protein stability. This interaction is enhanced by Tip60-mediated acetylation of USP26 at K134, which increases USP26 binding affinity to BAG3. Co-IP, ubiquitination assay, acetylation assay (Tip60), site-directed mutagenesis (K134), protein stability (half-life) assay Cancer letters Medium 38880224
2020 Elevated cellular ROS levels suppress USP26 deubiquitinase activity, leading to increased ubiquitination and proteasomal degradation of AR and ARv7 in prostate cancer cells, thereby increasing enzalutamide sensitivity. In vitro deubiquitinating enzyme activity assay, ROS measurement (dihydroethidium staining), ubiquitination assay Cancers Medium 32235588
2020 RAC1B promotes USP26 transcriptional induction, which in turn deubiquitinates and stabilizes SMAD7 protein, enabling SMAD7-mediated suppression of ALK5 and TGF-β1-induced cell migration in mesenchymal-type carcinoma cells. RNAi knockdown epistasis, western blot, ALK5 promoter reporter, cell migration assay Cancers Medium 32545415
2020 USP26 interacts with AR by Co-IP and deubiquitinates AR in Leydig cells (TM3), upregulating CCND1 and SPATA46 and decreasing TP73, promoting G1-G2 cell cycle transition and Leydig cell proliferation through the AR signaling pathway. Co-IP, immunofluorescence, western blot, flow cytometry cell cycle assay Advances in clinical and experimental medicine Low 33064378
2023 USP26 is the sole DUB identified from a DUB library screen that associates with KLF6. USP26 interacts with KLF6 (interaction domain mapped to residues 285-913 of USP26), deubiquitinates it, and prolongs KLF6 protein stability, inhibiting proliferation and migration of HeLa cells. DUB library screen, Co-IP (domain mapping), ubiquitination assay, half-life assay, shRNA knockdown, proliferation/migration assay Computers in biology and medicine Medium 38064851
2025 In osteoblasts, USP26 loss decreases H3K18 lactylation at the KSRP promoter, reducing KSRP expression and decreasing alternative splicing of FSTL1 mRNA, leading to elevated FSTL1 expression, insulin resistance, and multi-organ fibrosis. Osteoblast-specific Usp26 conditional KO mouse, ChIP (H3K18LA), RT-PCR (alternative splicing), metabolic and fibrosis phenotyping Advanced science Medium 41417635
2025 In osteoblasts, USP26 prevents ubiquitin-mediated degradation of IL4I1. Loss of USP26 in osteoblasts collapses IL4I1-mediated tryptophan metabolism (reducing indole-3-acetic acid production), impairing B lymphopoiesis and increasing susceptibility to sepsis. Osteoblast-specific Usp26 conditional KO mouse, targeted metabolomics, transcriptomics, in vivo/in vitro IL4I1 supplementation/inhibition, bone-targeting exosome delivery Journal of advanced research Medium 41687771
2025 USP26 interacts with and stabilizes c-Myc by suppressing its polyubiquitination and degradation, promoting aerobic glycolysis and proliferation in gastric cancer cells. Co-IP, ubiquitination assay, shRNA knockdown, proliferation/glycolysis assay DNA and cell biology Low 41125405
2014 USP26 protein colocalizes with androgen receptor in human testis, predominantly in Leydig cell nuclei (and to a lesser degree in spermatogonia, primary spermatocytes, round spermatids, and Sertoli cells), as established by immunofluorescence colocalization in human testis tissue. Immunofluorescence colocalization in formalin-fixed/paraffin-embedded and frozen human testis tissue PloS one Medium 24922532

Source papers

Stage 0 corpus · 45 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2005 Possible role of USP26 in patients with severely impaired spermatogenesis. European journal of human genetics : EJHG 76 15562280
2010 The deubiquitinating enzyme USP26 is a regulator of androgen receptor signaling. Molecular cancer research : MCR 73 20501646
2015 The de-ubiquitylating enzymes USP26 and USP37 regulate homologous recombination by counteracting RAP80. Nucleic acids research 64 26101254
2017 USP26 regulates TGF-β signaling by deubiquitinating and stabilizing SMAD7. EMBO reports 61 28381482
2019 USP26 promotes esophageal squamous cell carcinoma metastasis through stabilizing Snail. Cancer letters 48 30763716
2006 Haplotypes, mutations and male fertility: the story of the testis-specific ubiquitin protease USP26. Molecular human reproduction 36 16888075
2016 A Novel Missense Mutation in USP26 Gene Is Associated With Nonobstructive Azoospermia. Reproductive sciences (Thousand Oaks, Calif.) 33 27089915
2017 USP26 functions as a negative regulator of cellular reprogramming by stabilising PRC1 complex components. Nature communications 32 28839133
2008 USP26 gene variations in fertile and infertile men. Human reproduction (Oxford, England) 32 18927127
2006 Alterations of the USP26 gene in Caucasian men. International journal of andrology 31 17121659
2013 Ubiquitin-specific protease (USP26) gene alterations associated with male infertility and recurrent pregnancy loss (RPL) in Iranian infertile patients. Journal of assisted reproduction and genetics 29 23779098
2008 Association of USP26 haplotypes in men in Taiwan, China with severe spermatogenic defect. Asian journal of andrology 28 18958354
2022 USP26 promotes anaplastic thyroid cancer progression by stabilizing TAZ. Cell death & disease 27 35397626
2019 Usp26 mutation in mice leads to defective spermatogenesis depending on genetic background. Scientific reports 27 31551464
2014 Ubiquitin Specific Protease 26 (USP26) expression analysis in human testicular and extragonadal tissues indicates diverse action of USP26 in cell differentiation and tumorigenesis. PloS one 26 24922532
2021 Paternal USP26 mutations raise Klinefelter syndrome risk in the offspring of mice and humans. The EMBO journal 21 33978233
2015 Evidence from enzymatic and meta-analyses does not support a direct association between USP26 gene variants and male infertility. Andrology 20 25755145
2024 USP26 Combats Age-Related Declines in Self-Renewal and Multipotent Differentiation of BMSC by Maintaining Mitochondrial Homeostasis. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 19 39377219
2019 Ubiquitin-specific protease 26 (USP26) is not essential for mouse gametogenesis and fertility. Chromosoma 19 30887115
2010 Association between ubiquitin-specific protease USP26 polymorphism and male infertility in Chinese men. Clinica chimica acta; international journal of clinical chemistry 19 21147082
2008 Sequence analysis of the X-linked USP26 gene in severe male factor infertility patients and fertile controls. Fertility and sterility 19 18377898
2016 The testis-specific USP26 is a deubiquitinating enzyme of the ubiquitin ligase Mdm2. Biochemical and biophysical research communications 17 27810359
2016 Single nucleotide polymorphisms of USP26 in azoospermic men. Systems biology in reproductive medicine 16 27726449
2024 USP26 promotes colorectal cancer tumorigenesis by restraining PRKN-mediated mitophagy. Oncogene 15 38565942
2021 Novel Mutations in X-Linked, USP26-Induced Asthenoteratozoospermia and Male Infertility. Cells 15 34202084
2020 Preclinical Study Using ABT263 to Increase Enzalutamide Sensitivity to Suppress Prostate Cancer Progression Via Targeting BCL2/ROS/USP26 Axis Through Altering ARv7 Protein Degradation. Cancers 15 32235588
2009 The expression of Usp26 gene in mouse testis and brain. Asian journal of andrology 15 19503076
2017 The impacts of nineteen mutations on the enzymatic activity of USP26. Gene 12 29111204
2020 Novel mutation in USP26 associated with azoospermia in a Sertoli cell-only syndrome patient. Molecular genetics & genomic medicine 11 32410375
2024 USP26 as a hepatitis B virus-induced deubiquitinase primes hepatocellular carcinogenesis by epigenetic remodeling. Nature communications 10 39251623
2020 Targeting deubiquitinating enzyme USP26 by microRNA-203 regulates Snail1's pro-metastatic functions in esophageal cancer. Cancer cell international 10 32760222
2020 USP26 deubiquitinates androgen receptor (AR) in the maintenance of sperm maturation and spermatogenesis through the androgen receptor signaling pathway. Advances in clinical and experimental medicine : official organ Wroclaw Medical University 10 33064378
2024 Acetylation-dependent deubiquitinase USP26 stabilizes BAG3 to promote breast cancer progression. Cancer letters 8 38880224
2020 RAC1B Induces SMAD7 via USP26 to Suppress TGFβ1-Dependent Cell Migration in Mesenchymal-Subtype Carcinoma Cells. Cancers 8 32545415
2023 Machine learning-based classification of deubiquitinase USP26 and its cell proliferation inhibition through stabilizing KLF6 in cervical cancer. Computers in biology and medicine 7 38064851
2022 An RNF12-USP26 amplification loop drives germ cell specification and is disrupted by disease-associated mutations. Science signaling 7 35857630
2022 The association between mutations in ubiquitin-specific protease 26 (USP26) and male infertility: a systematic review and meta-analysis. Asian journal of andrology 5 35074940
2012 [Polymorphism of Usp26 correlates with idiopathic male infertility]. Zhonghua nan ke xue = National journal of andrology 5 22568204
2021 USP26: a genetic risk factor for sperm X-Y aneuploidy. The EMBO journal 4 34031897
2010 [Mutation of the USP26 gene in spermatogenesis dysfunction]. Zhonghua nan ke xue = National journal of andrology 4 20180409
2025 Activating the Osteoblastic USP26 Pathway Alleviates Multi-Organ Fibrosis by Decreasing Insulin Resistance. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 2 41417635
2026 Osteoblastic USP26 regulates B lymphopoiesis by endogenous tryptophan metabolites. Journal of advanced research 1 41687771
2025 A novel candidate missense variant in the catalytic domain of USP26 associated with asthenoteratozoospermia. Gene 1 41423141
2024 USP26 suppresses type I interferon signaling by targeting TRAF3 for deubiquitination. PloS one 1 39058724
2025 USP26 Promotes Cell Proliferation of Gastric Cancer by Stabilizing c-Myc. DNA and cell biology 0 41125405

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